Ed wants to understand the ground truth of the brain – what are the building blocks and how do they interact. We need to map the brain using expansion microscopy, then control and observe high speed dynamics using technologies like optogenetics and fluorescent imaging. There are many unique challenges that make this difficult. Neurons have nanoscale complexity and yet span centimeters of distance. Many neuronal phenomena operate at millisecond scales.
Expansion microscopy attempts to make it easier to view the brain by permeating neural structures with polymer chains. These polymers can be triggered to expand, pushing cellular structures apart while maintaining relative distances between them. It essentially magnifies objects while preserving nanoscale detail.
Color coding brain cells is another useful visualization tool. The Brainbow technique creates unique coloration from neuron to neuron, making it much easier to differentiate axon trails and map out the connectome. This technique can be enhanced with expansion microscopy to create extremely high resolution, high contrast imagery of the connectome.
Optogenetics is a technology that makes it possible to control the brain with light. Bacteriorhodopsins convert light energy into chemical energy. Derivatives of these proteins can be generated in neurons via gene therapy to allow light to alter their signaling processes. There are exciting opportunities on the horizon for therapies based on these mechanisms.
Imaging brain activity is difficult. There is no molecule in the natural world that we can use to report brain activity with high fidelity. Ed is attempting to use directed evolution to produce a fluorescent indicator of neural activity. He has produced a molecule called Archon to identify neural activity using an infrared laser. Imaging large fields of neuron activity could be possible using this material.
Combining these technologies together makes it possible to unlock many more secrets of the brain.
We need even better tools to visualize processes in the brain and figure out how to control those processes.